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2.
Gastroenterology ; 162(7):S-1008, 2022.
Article in English | EMBASE | ID: covidwho-1967396

ABSTRACT

BACKGROUND: Immune-modulating medications for inflammatory bowel diseases (IBD) have been associated with suboptimal vaccine responses. There is conflicting data with SARS-CoV-2 vaccination. METHODS: We measured SARS-CoV-2 vaccine immunogenicity at 2 weeks post 2nd mRNA vaccine in IBD patients as compared to normal healthy donors (NHD). We measured humoral immune responses to SARS-CoV-2: anti-spike Immunoglobulin G (IgG) and anti-receptor binding domain (RBD) IgG were measured by ELISA, and neutralizing antibody titers were measured using recombinant, reporter SARS-CoV-2. Antigen specific memory B cells were measured using recombinant SARS-CoV-2 proteins. Activation induced marker T cell (AIM) assays were performed using SARS-CoV-2 spike megapools. Immunophenotyping was performed by flow cytometry. RESULTS: We enrolled 29 patients with IBD (19 with Crohn's disease, 10 with ulcerative colitis) on infliximab (IFX) monotherapy (N=9), IFX combination therapy with a thiopurine (N=9), vedolizumab monotherapy (N= 11) as compared to matched NHD (N=12). At 2 weeks post vaccination, all subjects made detectable anti-spike IgG and anti-RBD IgG. There were no differences in anti-spike IgG titers among the different groups. IBD patients on IFX monotherapy, but not IBD patients on IFX combination therapy or vedolizumab monotherapy, had lower anti-RBD and neutralization titers as compared to NHD (p-value: 0.041 and 0.023, respectively) (Fig. 1). There were no significant differences in the percentage of spike-specific or RBD-specific memory B cells in IBD patients as compared to NHD (Fig. 1). There were no differences in the percentage of spike-specific CD4+ or CD8+ T cells in all IBD patients as compared to NHDs (Fig. 2). CONCLUSIONS: We demonstrate overall comparable and perserved cell-mediated immunity to SARS-CoV-2 vaccination in a small cohort of IBD patients treated with a range of different immune-modulating medications as compared to healthy controls. Larger numbers of patients are needed to validate these findings.

3.
Gastroenterology ; 162(7):S-160, 2022.
Article in English | EMBASE | ID: covidwho-1967250

ABSTRACT

Background: Vaccine-induced protection against SARS-CoV-2 infection is predominantly mediated by humoral immunity;protection against disease progression is primarily determined by cellular immunity. Patients with inflammatory bowel disease (IBD) have high rates of post-vaccination anti-Spike IgG [IgG(S)] seroconversion, but postvaccination immune responses relative to non-IBD controls have not been well described. We aimed to assess post-vaccination humoral (antibody) and cellular (T-cell) responses in IBD relative to healthcare worker (HCW) controls. Methods: We evaluated IBD patients enrolled in a US registry referred from 26 centers at 2, 8, and 16 weeks after completing 2 doses of SARSCoV- 2 mRNA vaccination and compared results to non-IBD non-immunosuppressed HCW participating in a parallel study. We analyzed plasma antibodies to the receptor binding domain of the viral spike protein using the SARS-CoV-2 IgG-II assay (Abbott Labs, Abbott Park, IL);IgG(S) > 50 AU/mL was defined as positive. Those with prior COVID were excluded. We also performed T-cell clonal analysis by T-cell receptor (TCR) immunosequencing at 8 weeks (Adaptive Biotechnologies, Seattle, WA). The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets. Analyses were adjusted for age, sex and vaccine type. Results: Overall, 1805 subjects were included (IBD n=1074 (65% Crohn's disease, 35% ulcerative colitis);HCW n=731). Age and sex were similar between both cohorts;Hispanic ethnicity and Asian race were less common among IBD than HCW (Table). Vaccine type included BNT162b2 (Pfizer) (75% of IBD, 98% of HCW) and the remainder mRNA-1274 (Moderna). IBD treatments included anti- TNF (46%), other biologics (33%), other immune suppressing therapy (9%), and no immune suppression (12%). Postvaccination antibody levels were lower among IBD than HCW both before and after adjusting for vaccine type (p<0.0001 each timepoint;Figure). After further restricting the IBD cohort to those on no immune-suppressive therapies, antibodies remained lower in IBD vs HCW at 2w (p=0.008) and 8w (p<0.0001), but not 16w (p=0.07). Among 321 subjects with available whole cell samples at 8 weeks (IBD n=163, HCW =158), Spikespecific TCR responses were similar between IBD and HCW for both clonal breadth and depth in both unadjusted and adjusted analyses;sub-analyses of those on biologics yielded similar results. Conclusion: Patients with IBD have dampened humoral responses, but similar cellular responses, after SARS-CoV-2 mRNA vaccination relative to HCW. These findings suggest a potentially greater risk of infection, but not of disease progression, among those with IBD, and should be considered to help guide booster dosing strategies for the IBD population. (Figure Presented) (Figure Presented) Figure: Post-vaccination immune responses: (A) Antibody responses are lower in IBD relative to non-IBD healthcare workers at 2, 8, and 16 weeks (p<0.0001 at each timepoint). In contrast, post-vaccination Spike-specific T-cell receptor clonal breadth (B1) and clonal depth (B2) at 8 weeks are similar in IBD compared to healthcare workers.

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